Maintaining the balance between bleeding and thrombosis remains one of the greatest challenges facing the biomedical community. Excessive bleeding is an important medical issue. For example, post partum bleeding represents a leading cause of maternal mortality and causes serious morbidity in developing countries. Individuals with genetic bleeding disorders, such as hemophilia, have a decreased ability to clot blood because of deficiencies in certain coagulation factors.
On the other end of the spectrum, excessive clotting, or thrombosis, is a major complication of surgery and is integrally involved in atherosclerosis, obesity, infection, diabetes, cancer, and autoimmune disorders. Over the last decade, significant advances have been made in understanding the molecular basis of bleeding and thrombotic disorders; however, a large portion of the observed variability remains unknown.
Parallel with these discoveries, there has been a rapid development of new drugs such as recombinant proteins for replacement and interventional therapies. Interestingly, what remains strikingly deficient in clinical hematology are techniques to diagnose a very broad range of disorders of both deficient and excessive clotting as well as to monitor the effects of therapeutic interventions.
The formation of a stable fibrin network is necessary for hemostasis, which requires fibrinogen conversion to fibrin. In purified systems containing only thrombin and fibrinogen, it has been shown that fibrin polymerization can only occur in a narrow set of conditions that are defined by the rate of thrombin formation and the shear rate (Neeves et al., Biophysical Journal, 2010, 98; 1344-1352). Most coagulation assays do not account for the interplay between flow and surface reactions, which could affect clot properties like fiber thickness, fibrin clot height, fiber alignment with flow, and resistance to lysis. These properties can be useful in differentiating plasma clots of healthy individuals from those with thrombotic or haemostatic disorders.
Diagnosing the severity of bleeding a disorder is impossible with current bleeding assays, particularly because most current bleeding assays test for either platelet function and/or platelet coagulation using whole blood, however, these assays do not allow for the use plasma. Additionally, most existing solutions do not properly create an environment which properly simulates a natural human wound or point of bleeding. Also, most of these conventional assays occur under static, or no flow, conditions. Since blood is a moving fluid, however, there are several advantages to studying it under flow in bleeding diagnostics.